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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05201547


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT05201547
Ethics application status
Date submitted
22/11/2021
Date registered
21/01/2022
Date last updated
22/05/2024

Titles & IDs
Public title
Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line
Scientific title
Randomized Phase III Trial in MMR Deficient Endometrial Cancer Patients Comparing Chemotherapy Alone Versus Dostarlimab in First Line Advanced/Metastatic Setting
Secondary ID [1] 0 0
GINECO-EN105b
Universal Trial Number (UTN)
Trial acronym
DOMENICA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Carboplatin-Paclitaxel
Treatment: Drugs - Dostarlimab

Experimental: Arm A: Dostarlimab 500 mg, every 3 weeks, 4 cycles and then 1000 mg every 6 weeks -

Experimental: Arm B: Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2, every 3 weeks, 6 cycles. -


Treatment: Drugs: Carboplatin-Paclitaxel
Chemotherapy will be administered by intravenous infusion. Carboplatin AUC 5-6 + Pacltaxel 175 mg/m² every 3 weeks. Total duration of treatment: 6 cycles

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered through a 30-minute infusion at a dose of 500 mg Q3W from Cycle 1 through Cycle 4 and at a dose of 1,000 mg Q6W thereafter, beginning at Cycle 5 Day 1 up to a maximum of 2 years.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years.
Secondary outcome [1] 0 0
Overall Survival (OS) (key secondary endpoint)
Timepoint [1] 0 0
from the date of randomization until death due to any cause, assessed up to 5 years
Secondary outcome [2] 0 0
Progression Free Survival 2 (PFS2)
Timepoint [2] 0 0
from the date of randomization until second objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years
Secondary outcome [3] 0 0
Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version)
Timepoint [3] 0 0
through study completion, an average of 5 years
Secondary outcome [4] 0 0
To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30)
Timepoint [4] 0 0
Defined as the Global Health Status score from the EORTC QLQ C30 at 18 weeks, assessed up to 5 years
Secondary outcome [5] 0 0
To assess the quantity of peripheral neuropathy event induced by chemotherapy based on EORTC QLQ-CIPN 20 (Quality of Life questionnaire-Chemotherapy induced peripheral neuropathy 20)
Timepoint [5] 0 0
Defined as the Global Health Status score from the EORTC QLQ-CIP20 at 18 weeks, assessed up to 5 years
Secondary outcome [6] 0 0
To assess the effects of treatment on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based EORTC QLQ-EN24 (Quality of Life Questionnaire - Endometrial Cancer Module)
Timepoint [6] 0 0
Defined as the Global Health Status score from the EORTC QLQ-EN24 at 18 weeks, assessed up to 5 years
Secondary outcome [7] 0 0
To assess the status of health for patients with endometrial cancer based on EUROQOL EQ-5D (Descriptive system)
Timepoint [7] 0 0
Defined as the Global Health Status score from the EUROQOL EQ-5D at 18 weeks, assessed up to 5 years
Secondary outcome [8] 0 0
Best Objective Response Rate (ORR)
Timepoint [8] 0 0
from the date of randomization until best objective response based on RECIST 1.1, assessed up to 5 years
Secondary outcome [9] 0 0
Disease Control Rate (DCR)
Timepoint [9] 0 0
from the date of randomization until response or stable disease per RECIST 1.1, assessed up to 5 years
Secondary outcome [10] 0 0
Duration of Response Rate (DoR)
Timepoint [10] 0 0
from the time of initial response until documented tumor progression ,assessed up to 5 years
Secondary outcome [11] 0 0
Safety and number of adverse events
Timepoint [11] 0 0
From date of randomization until end of study, assessed up to 6 years
Secondary outcome [12] 0 0
Tolerability to the treatment
Timepoint [12] 0 0
From date of randomization until end of study, assessed up to 6 years
Secondary outcome [13] 0 0
Time to first and second Subsequent Treatment
Timepoint [13] 0 0
from the date of randomization to date of event, assessed up to an average of 5 years
Secondary outcome [14] 0 0
To determine the immunogenicity of dostarlimab
Timepoint [14] 0 0
from randomisation to 12 weeks after end of treatment, assessed at study end

Eligibility
Key inclusion criteria
- Patients must fulfil all the following criteria:

1. Female patient is at least 18 years of age,

2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol
requirements.

3. Patient with histologically proven endometrial adenocarcinoma with recurrent or
advanced disease.

4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0 or 1.

5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first recurrent
endometrial cancer (see International Federation of Gynecology and Obstetrics
staging FIGO Staging 18.1) without curative treatment by radiation therapy or
surgery alone or in combination, and meet at least one of the following
situations:

1. Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative
intent surgery or radiation.

2. Patient has first recurrent disease and is chemotherapy naïve for this 1st
recurrence or metastatic setting.

3. Patient has recurrent disease and is chemotherapy naïve for recurrence or
advanced /metastatic setting.

4. Patient may have received prior irradiation for advanced endometrial cancer
with or without radio-sensitizing chemotherapy if > 3 weeks before the start
of the study

6. Patient with evaluable disease (measurable and not measurable disease) according
to RECIST 1.1

7. Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for
the primary cancer and had a recurrence = 6 months after completing treatment
(first recurrence only).

8. All histologic subtypes of endometrial adenocarcinoma could be included if
MMRd/MSI-H

9. MMRd/MSI-H tumor (first diagnosed by routine local IHC performed either on
primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory for
inclusion. A central confirmation will be done before inclusion; in case of
ambiguous result of central IHC (lack of positive internal control, heterogeneous
loss of MMR protein expression), MSI-H status will be assessed by PCR/NGS

10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or
PCR/ NGS, and additional block(s) for Translational Research

11. . Patient could have been previously treated with hormone therapy, for the
metastatic/advanced disease 12) Patient may have received pelvic and lombo-aortic
external beam +/- vaginal brachytherapy

13. Patient has adequate organ function, defined as follows:

a) Absolute neutrophil count = 1,500 cells/µL b) Platelets = 100,000 cells/µL c)
Haemoglobin = 9 g/dL or = 5.6 mmol/L d) Serum creatinine = 1.5× upper limit of normal
(ULN) or calculated creatinine clearance = 50 mL/min using the Cockcroft-Gault
equation for patients with creatinine levels > 1.5× institutional ULN e) Total
bilirubin = 1.5× ULN (= 2.0 x ULN in patients with known Gilbert's syndrome) or direct
bilirubin = 1× ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) = 2.5× ULN unless liver metastases are present, in which case they must be = 5×
ULN g) International normalized ratio or prothrombin time (PT) =1.5× ULN and activated
partial thromboplastin time =1.5× ULN. Patients receiving anticoagulant therapy must
have a PT or partial thromboplastin within the therapeutic range of intended use of
anticoagulants.

14. Patient must have a negative serum pregnancy test within 72 hours of the first
dose of study medication, unless they are of nonchildbearing potential.
Nonchildbearing potential is defined as follows:

1. Patient is = 45 years of age and has not had menses for > 1 year.

2. A follicle-stimulating hormone value in the postmenopausal range upon screening
evaluation if amenorrhoeic for < 2 years without a hysterectomy and oophorectomy.

3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:

- Documented hysterectomy or oophorectomy must be confirmed with medical records of the
actual procedure or confirmed by an ultrasound, MRI, or CT scan.

- Tubal ligation must be confirmed with medical records of the actual procedure;
otherwise, the patient must fulfil the criteria in Inclusion Criterion 14.

- Information must be captured appropriately within the site's source documents. 15.
Patient of childbearing potential must agree to use a highly effective method of
contraception (section 18.9) with their partners starting from time of consent through
150 days after the last dose of study treatment. Note: Abstinence is acceptable if
this is the established and preferred contraception for the patient (Information must
be captured appropriately within the site's source documents).
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients are to be excluded from the study if they meet any of the following criteria:

1. Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary Stage
III or IV disease and has had a recurrence or PD within 6 months of completing
this chemotherapy treatment prior to entering the study.

Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do
not exclude patients from study participation.

2. Patient has had > 1 recurrence of endometrial cancer, treated with chemotherapy.
Surgery of the recurrence is allowed.

3. Patient previously treated with systemic chemotherapy for non-curable advanced
disease or metastatic disease

4. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
agent.

5. Patient has received prior anticancer therapy for (advanced or metastatic disease
(targeted therapies, hormonal therapy, radiotherapy) within 21 days or < 5 times
the half-life of the most recent therapy prior to Study Day 1, whichever is
shorter Note: Palliative radiation therapy to a small field = 1 week prior to Day
1 of study treatment may be allowed.

6. Patient with contraindication to chemotherapy or checkpoint inhibitor treatments

7. Patient has a concomitant malignancy, or patient has a prior non-endometrial
invasive malignancy who has been disease-free for < 3 years or who received any
active treatment in the last 3 years for that malignancy. Non-melanoma skin
cancer is allowed.

8. Patient has known uncontrolled central nervous system metastases, carcinomatosis
meningitis, or both. Note: Patients with previously treated brain metastases may
participate provided they are stable (without evidence of disease progression by
imaging [using the identical imaging modality for each assessment, either MRI or
CT scan] for at least 4 weeks prior to the first dose of study treatment and any
neurologic symptoms have returned to baseline), have no evidence of new or
enlarging brain metastases, and have not been using steroids for at least 7 days
prior to study treatment. Carcinomatous meningitis precludes a patient from study
participation regardless of clinical stability.

9. Patient has a known history of human immunodeficiency virus (HIV; HIV 1 or 2
antibodies).

10. Patient has known active viral infection of hepatitis B (eg, hepatitis B surface
antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid
[qualitative] detection).

11. Patient has an active autoimmune disease that has required systemic treatment in
the past 2 years. Replacement therapy is not considered a form of systemic
therapy (eg, thyroid hormone or insulin).

12. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of systemic immunosuppressive therapy within 7 days
prior to the first dose of study treatment.

13. Patient has not recovered (ie, to Grade = 1 or to baseline) from cytotoxic
therapy-induced adverse events (AEs).

Note: Patients with Grade = 2 neuropathy, Grade = 2 alopecia, or Grade = 2
fatigue are an exception to this criterion and may qualify for the study.

14. Patient has not recovered adequately from AEs or complications from any major
surgery prior to starting therapy.

15. Patient has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab
components or excipients.

16. Patient is currently participating and receiving study treatment or has
participated in a study of an investigational agent and received study treatment
or used an investigational device within 4 weeks of the first dose of treatment.

17. Patient is considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease, or active infection requiring systemic
therapy. Specific examples include, but are not limited to, active,
non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within
90 days) myocardial infarction; uncontrolled major seizure disorder; unstable
spinal cord compression; superior vena cava syndrome; or any psychiatric or
substance abuse disorders that would interfere with cooperation with the
requirements of the study (including obtaining informed consent).

18. Use of any of the following immunomodulatory agents within 30 days prior to the
first dose of study drug:

- Systemic corticosteroids (at dose higher than 10 mg/day equivalent
prednisone); if systemic corticoid use at higher dose, corticoid must be
stopped at least 7 days before study treatment start

- Interferons

- Interleukins

- Live vaccine Note: Examples of live vaccines include, but are not limited
to, the following: measles, mumps, rubella, varicella/zoster, yellow fever,
rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed as other killed
vaccines, if done at least 2 weeks prior the first dose of study drug;
however, intranasal influenza vaccines (eg, FluMist®) are live attenuated
vaccines and are not allowed.

19. Patient is pregnant or breastfeeding or is expecting to conceive children within
the projected duration of the study, starting with the screening visit through
180 days after the last dose of study treatment, or lactating woman.

20. Patients who had an allogenic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2029
Actual
Sample size
Target
260
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Toronto
Country [2] 0 0
France
State/province [2] 0 0
Angers
Country [3] 0 0
France
State/province [3] 0 0
Avignon
Country [4] 0 0
France
State/province [4] 0 0
Besançon
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux
Country [6] 0 0
France
State/province [6] 0 0
Brest
Country [7] 0 0
France
State/province [7] 0 0
Caen
Country [8] 0 0
France
State/province [8] 0 0
Chambray-lès-Tours
Country [9] 0 0
France
State/province [9] 0 0
Clermont-Ferrand
Country [10] 0 0
France
State/province [10] 0 0
Créteil
Country [11] 0 0
France
State/province [11] 0 0
Dijon
Country [12] 0 0
France
State/province [12] 0 0
Le Mans
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Marseille
Country [16] 0 0
France
State/province [16] 0 0
Mont de Marsan
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Mougins
Country [19] 0 0
France
State/province [19] 0 0
Nancy
Country [20] 0 0
France
State/province [20] 0 0
Nantes
Country [21] 0 0
France
State/province [21] 0 0
Nice
Country [22] 0 0
France
State/province [22] 0 0
Nîmes
Country [23] 0 0
France
State/province [23] 0 0
Orléans
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
Plérin
Country [26] 0 0
France
State/province [26] 0 0
Poitiers
Country [27] 0 0
France
State/province [27] 0 0
Quimper
Country [28] 0 0
France
State/province [28] 0 0
Reims
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Rouen
Country [31] 0 0
France
State/province [31] 0 0
Saint-Herblain
Country [32] 0 0
France
State/province [32] 0 0
Saint-Étienne
Country [33] 0 0
France
State/province [33] 0 0
Strasbourg
Country [34] 0 0
France
State/province [34] 0 0
Toulouse
Country [35] 0 0
France
State/province [35] 0 0
Tours
Country [36] 0 0
France
State/province [36] 0 0
Vandœuvre-lès-Nancy
Country [37] 0 0
France
State/province [37] 0 0
Villejuif
Country [38] 0 0
Singapore
State/province [38] 0 0
Singapore
Country [39] 0 0
Spain
State/province [39] 0 0
Alicante
Country [40] 0 0
Spain
State/province [40] 0 0
Badalona
Country [41] 0 0
Spain
State/province [41] 0 0
Córdoba
Country [42] 0 0
Spain
State/province [42] 0 0
León
Country [43] 0 0
Spain
State/province [43] 0 0
Palma De Mallorca
Country [44] 0 0
Spain
State/province [44] 0 0
Palma
Country [45] 0 0
Spain
State/province [45] 0 0
Santiago De Compostela
Country [46] 0 0
Spain
State/province [46] 0 0
Valencia
Country [47] 0 0
Spain
State/province [47] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Other
Name
ARCAGY/ GINECO GROUP
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab
versus carboplatin-paclitaxel in patients with MMR deficient relapse or advanced endometrial
cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05201547
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Florence JOLY, Pr
Address 0 0
Centre François Baclesse
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ophélie BACONNET
Address 0 0
Country 0 0
Phone 0 0
01 84 85 20 20
Fax 0 0
Email 0 0
Domenica@arcagy.org
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05201547

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 171
Calvary Mater Newcastle
Recruitment postcode(s) [1] 172
2298
Funding & Sponsors
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Primary sponsor address
Level 6, Lifehouse 119-143 Missenden Road Camperdown NSW 2050
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 71
Hunter New England HREC
Address [1] 71
Country [1] 71
Australia
Date submitted for ethics approval [1] 71
01/09/2023
Approval date [1] 71
22/09/2023
Ethics approval number [1] 71
2023/ETH01687
 
Public notes

Contacts
Principal investigator
Title 421 0
A/Prof
Name 421 0
Alison Davis
Address 421 0
Country 421 0
Australia
Phone 421 0
Fax 421 0
Email 421 0
alison.davis@act.gov.au
Contact person for public queries
Title 422 0
Mrs
Name 422 0
Lisa Bailey
Address 422 0
Country 422 0
Australia
Phone 422 0
Fax 422 0
Email 422 0
domenica@anzgog.org.au
Contact person for scientific queries
Title 423 0
Mrs
Name 423 0
Lisa Bailey
Address 423 0
Country 423 0
Australia
Phone 423 0
Fax 423 0
Email 423 0
domenica@anzgog.org.au